Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality

Seng-Wei Ooi; Shu-Tin Yeh; Ya-Hui Chang; Chung-Yi Li; Hua-Fen Chen

doi:10.1371/journal.pone.0288360

Peer Review History

Original SubmissionFebruary 16, 2023
22 May 2023 Decision Letter - Fateen Ata, Editor PONE-D-23-02045Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortalityPLOS ONE Dear Dr. Author, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== ACADEMIC EDITOR: Please review the attached reviewer comments and address the concerns Please submit your revised manuscript by Jul 06 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: Yes Reviewer #3: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Seng-Wei Ooi et al. investigated the relationship between several levels of hypoglycemia and all-cause or cardiovascular mortality and between mean HbA1c levels and all-cause or cardiovascular mortality in 27,932 patients with T2D in Taiwan (2008-2018). They found that significant increased risk of all-cause mortality was associated with only most severe level 3 hypoglycemia levels in patients with T2D. In addition, T2D patients with mean HbA1c ≥ 9% manifested significant higher all-cause and cardiovascular mortality than T2D patients with mean HbA1c < 9%. This study was well conducted and the observed results provided considerable clinical significance in management of patients with T2D. Since serum lipid disorders are critical problem for the development of cardiovascular events and its mortality, in addition to LDL-C, data of triglycerides and HDL-C are needed for the assessment. Reviewer #2: Thanks authors for carried out this study . there are some concern which authors mentioned in limitation which is acceptable I would suggest author to bring more pathophysiological explanations about how hypoglycemic could increase the risk of mortality ; in discussion section only other's studies result compared , but needs more explanations Reviewer #3: The paper showed the relationship between various levels of hypoglycemia and mean glycated hemoglobin A1c (HbA1c) achieved with all-cause and cardiovascular mortality in patients with T2D.They reveal that patients with level 3 hypoglycemia marginally increased all-cause mortality, but not cardiovascular mortality. Hypoglycemia in patients with higher mean HbA1c rather than low mean HbA1c were associated with an elevated risk of all-cause or cardiovascular mortality, which is of interest. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. 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Revision 1
15 Jun 2023 Author Response Response to the editor and the reviewers Response to the editor 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. Authors’ reply We tried our best to revise the manuscript according to PLOS ONE's style requirements. 2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed: 1. 10.7717/peerj.14609 (shaded with blue) 2. https://doi.org/10.1371/journal.pone.0272137 (shaded with yellow) 3. https://doi.org/10.1016/j.amjmed.2011.07.011 (shaded with green) In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Authors’ reply We used Microsoft Word to compare the current manuscript to our previous works with another manuscript, and to our best rephrase the duplicate text. We quoted all the works above mentioned (reference 14, 12, and 19 of the revised manuscript) 3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Authors’ reply We deleted the ethics statement apart from the Methods section (Please see the page 23, Lines 471-473 of the revised manuscript), and amended the ethics statement including the full name of the ethics committee/institutional review board(s) in methods section (Please see the page 5, Lines 116-118 of the revised manuscript). 4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. Authors’ reply The data sets analyzed during the current study are not publicly available because the restrictions are imposed by the Research Ethics Review Committee of Far Eastern Memorial Hospital. Although we cannot share the data publicly, the minimal datasets are available upon request from the Research Ethics Review Committee of Far Eastern Memorial Hospital repository (via: https://www.femh-irb.org/index.php/procedure). Application to the Research Ethics Review Committee of Far Eastern Memorial Hospital (contact via irb@mail.femh.org.tw, reference number 108008-F) is available for researchers. Response to the reviewer 1 1. Seng-Wei Ooi et al. investigated the relationship between several levels of hypoglycemia and all-cause or cardiovascular mortality and between mean HbA1c levels and all-cause or cardiovascular mortality in 27,932 patients with T2D in Taiwan (2008-2018). They found that significant increased risk of all-cause mortality was associated with only most severe level 3 hypoglycemia levels in patients with T2D. In addition, T2D patients with mean HbA1c ≥ 9% manifested significant higher all-cause and cardiovascular mortality than T2D patients with mean HbA1c < 9%. This study was well conducted and the observed results provided considerable clinical significance in management of patients with T2D. Since serum lipid disorders are critical problem for the development of cardiovascular events and its mortality, in addition to LDL-C, data of triglycerides and HDL-C are needed for the assessment. Authors’ reply We added data of triglycerides and HDL-C (Please see Page 6, Lines 147-148, Page 11, Table 1, of the revised manuscript) We also re-analyzed all the regression models with addition of triglycerides and HDL-C, and the results are presented in Tables 2 and 3 (Please see Page 13-14, Table 2 and Page 16-17, Table 3 of the revised manuscript). The response to the reviewer 2 1. Thanks authors for carried out this study . there are some concern which authors mentioned in limitation which is acceptable. I would suggest author to bring more pathophysiological explanations about how hypoglycemic could increase the risk of mortality ; in discussion section only other's studies result compared , but needs more explanations Authors’ reply We have revised the discussion section with addition of plausible pathophysiological mechanisms about how hypoglycemic could increase the risk of mortality. (Page 21, Lines 429-438 of the revised manuscript) The response to the reviewer 3 1. The paper showed the relationship between various levels of hypoglycemia and mean glycated hemoglobin A1c (HbA1c) achieved with all-cause and cardiovascular mortality in patients with T2D.They reveal that patients with level 3 hypoglycemia marginally increased all-cause mortality, but not cardiovascular mortality. Hypoglycemia in patients with higher mean HbA1c rather than low mean HbA1c were associated with an elevated risk of all-cause or cardiovascular mortality, which is of interest. Attachments Attachment Submitted filename: Response to the editor and the reviewers_20230615.docx https://doi.org/10.1371/journal.pone.0288360.r002
26 Jun 2023 Decision Letter - Fateen Ata, Editor Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality PONE-D-23-02045R1 Dear Dr. Chen We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Fateen Ata, MD Academic Editor PLOS ONE Additional Editor Comments (optional): All revisions by the reviewers have been considered and made by the authors in a satisfactory manner. Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: Ken-ichi Aihara ******** https://doi.org/10.1371/journal.pone.0288360.r003
Formally Accepted
5 Jul 2023 Acceptance Letter - Fateen Ata, Editor PONE-D-23-02045R1 Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality Dear Dr. Chen: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Fateen Ata Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0288360.r004

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